Shared Genetic Architecture and Causal Relationship between Serum 25-Hydroxyvitamin D and Bone Mineral Density DOI Creative Commons
Linna Sha, Li Zhang, Xunying Zhao

и другие.

The Journal of Clinical Endocrinology & Metabolism, Год журнала: 2024, Номер unknown

Опубликована: Окт. 21, 2024

Abstract Context Despite the well-established regulatory role of vitamin D in maintaining bone health, little is known about shared genetics and causality association between serum 25-hydroxyvitamin (25OHD) mineral density (BMD). Objective We aimed to investigate genetic architecture causal relationship 25OHD BMD, providing insights into their underlying biological mechanisms. Methods Leveraging individual-level data from UK Biobank (UKB) cohort summary-level genome-wide studies (GWASs) conducted on European individuals for (N = 417 580) estimated heel BMD (eBMD, N 426 824), we systematically elucidated eBMD through a comprehensive cross-trait design. Results lack global correlation (rg=−0.001; P .95), statistically significant local signal was discovered at 5p11-5q11.9. Two-sample mendelian randomization (MR) indicated no overall population (β=.003, 95% CI, −0.04 0.03; .93), while positive effects were observed males (β=.005, 0.00 0.01; .03) older (β=.009, 0.00∼0.02; .01) according one-sample MR. A total 49 pleiotropic single-nucleotide variations (SNVs), with 4 novel SNVs (rs1077151, rs79873740, rs12150353, rs4760401), identified, 95 gene-tissue pairs exhibited overlap, predominantly enriched nervous, digestive, exocrine/endocrine, cardiovascular systems. Protein-protein interaction analysis identified RPS9 RPL7A as hub genes. Conclusion This study illuminates potential health benefits enhancing levels mitigate risk osteoporosis among men than 65 years. It also unveils basis eBMD, offering valuable intricate pathways.

Язык: Английский

Shared Genetic Architecture and Causal Relationship between Serum 25-Hydroxyvitamin D and Bone Mineral Density DOI Creative Commons
Linna Sha, Li Zhang, Xunying Zhao

и другие.

The Journal of Clinical Endocrinology & Metabolism, Год журнала: 2024, Номер unknown

Опубликована: Окт. 21, 2024

Abstract Context Despite the well-established regulatory role of vitamin D in maintaining bone health, little is known about shared genetics and causality association between serum 25-hydroxyvitamin (25OHD) mineral density (BMD). Objective We aimed to investigate genetic architecture causal relationship 25OHD BMD, providing insights into their underlying biological mechanisms. Methods Leveraging individual-level data from UK Biobank (UKB) cohort summary-level genome-wide studies (GWASs) conducted on European individuals for (N = 417 580) estimated heel BMD (eBMD, N 426 824), we systematically elucidated eBMD through a comprehensive cross-trait design. Results lack global correlation (rg=−0.001; P .95), statistically significant local signal was discovered at 5p11-5q11.9. Two-sample mendelian randomization (MR) indicated no overall population (β=.003, 95% CI, −0.04 0.03; .93), while positive effects were observed males (β=.005, 0.00 0.01; .03) older (β=.009, 0.00∼0.02; .01) according one-sample MR. A total 49 pleiotropic single-nucleotide variations (SNVs), with 4 novel SNVs (rs1077151, rs79873740, rs12150353, rs4760401), identified, 95 gene-tissue pairs exhibited overlap, predominantly enriched nervous, digestive, exocrine/endocrine, cardiovascular systems. Protein-protein interaction analysis identified RPS9 RPL7A as hub genes. Conclusion This study illuminates potential health benefits enhancing levels mitigate risk osteoporosis among men than 65 years. It also unveils basis eBMD, offering valuable intricate pathways.

Язык: Английский

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